# US 2018/0024338 A1 · Multi-focal structured illumination microscopy systems and methods

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2018/0024338 A1
- Document ID: US20180024338A1
- Status: Published application
- Kind: A1
- Application number: 15/610,906
- Filed: 2017-06-01
- Published: 2018-01-25
- Earliest claimed: 2012-02-23
- Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Applicants: The United States of America, as represented by Secretary, Department of Health and Human Services
- Inventors: Hari Shroff; Andrew York
- Web page: https://patentgrep.com/patent/US20180024338A1

## CPC

- G02B 21/0072: {details concerning resolution or correction, including general design of CSOM objectives}
- G01N 21/6458: {Fluorescence microscopy (fluorescence microscopes per se G02B21/0076 and G02B21/16)}
- G02B 21/0032: {Optical details of illumination, e.g. light-sources, pinholes, beam splitters, slits, fibers (G02B21/0036 - G02B21/008; means for illumination of specimens in general G02B21/06)}
- G02B 21/0036: {Scanning details, e.g. scanning stages}
- G02B 21/004: {fixed arrays, e.g. switchable aperture arrays}
- G02B 21/0076: {arrangements using fluorescence or luminescence}
- G01N 2021/6478: {Special lenses}
- G01N 2201/0633: Directed, collimated illumination
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

A multi-focal selective illumination microscopy (SIM) system for generating multi-focal patterns of a sample is disclosed. The multi-focal SIM system performs a focusing, scaling and summing operation on each multi-focal pattern in a sequence of multi-focal patterns that completely scan the sample to produce a high resolution composite image.

## Claims

### Claim 1

A microscopy system comprising:
a light source for transmitting a single light beam;
a beam splitter for splitting the single light beam into a plurality of light beams forming a plurality of multi-focal patterns, wherein each of the multi-focal patterns defines a plurality of focal points;
a scanner for scanning the plurality of light beams that forms each of the multi-focal patterns onto a sample such that the sample generates a plurality of multi-focal fluorescent emissions in each of the multi-focal patterns that defines a plurality of fluorescence focal points;
a detector for collecting the plurality of multi-focal fluorescent emissions that results from each of the multi-focal patterns; and
a processing system for processing the plurality of multi-focal fluorescent emissions that results from each of the multi-focal patterns collected from the detector comprising:
a processor in operative communication with a database for storing the plurality of collected multi-focal fluorescent emissions resulting from the multi-focal patterns, wherein the processor removes out-of-focus fluorescent emissions for each of the plurality of fluorescent emission to leave only in-focus fluorescent emissions resulting from each of the plurality of multi-focal patterns, wherein the processor then scales the in-focus fluorescence emissions resulting from each of the plurality of multi-focal patterns in a local contraction operation in which each of the plurality of fluorescent focal points resulting from each of the multi-focal patterns maintains the same distance from another plurality of fluorescent focal points resulting from the multi-focal pattern as the plurality of fluorescent focal points contract to produce scaled, in-focus fluorescent emissions; wherein the processor sums each scaled, in-focus fluorescence emissions to produce a composite image.

### Claim 2 (depends on 1)

The microscopy system of claim 1, further comprising the processor executing a deconvolution operation for processing the plurality of multi-focal patterns with the scaled, in-focus fluorescent emissions.

### Claim 3 (depends on 1)

The microscopy system of claim 1, wherein the beam splitter is a digital micromirror device or a swept-field confocal unit, or a spinning-disk, or Nipkow confocal scan head.

### Claim 4 (depends on 1)

The microscopy system of claim 1, wherein the processing system executes an automatic lattice detection of each of the plurality of multi-focal patterns to determine the position of one or more illumination spots.

### Claim 5 (depends on 4)

The microscopy system of claim 4, wherein the automatic lattice detection determines a plurality of vectors to locate the position of each of the one or more illumination spots.

### Claim 6 (depends on 5)

The microscopy system of claim 5, wherein the plurality of vectors comprises lattice vectors, shift vectors, and/or offset vectors.

### Claim 7 (depends on 6)

The microscopy system of claim 6, wherein two of the lattice vectors specify a two-dimensional displacement between any two neighboring illumination spots.